Adenosine triphosphate accelerates recovery from hypoxic/hypoglycemic perturbation of guinea pig hippocampal neurotransmission via a P2 receptor

Aihara, Hideo; Fujiwara, Satoe; Mizuta, Ikuko; Tada, Hitoshi; Kanno, Takeshi; Tozaki, Hidetoshi; Nagai, Kazuo; Yajima, Yukio; Inoue, Kazuhide; Kondoh, Takeshi; Motooka, Yasuhiko; Nishizaki, Tomoyuki

doi:10.1016/s0006-8993(02)03185-2

Cited by 21 publications

(9 citation statements)

References 30 publications

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“…Studies on mammalian synapses have indicated that hypoxia may produce its effects on synaptic depression, in part, by altering the release of ATP and adenosine from presynaptic terminals (47)(48)(49). Our present findings suggest that a change in conductance of mitochondrial membranes is one of the earliest events in the neuronal response to hypoxia and suggest that the induced channel activity is closely linked to the change in transmission, perhaps by altering the flux of ATP, calcium, or other factors close to sites of exocytosis.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse

Jonas

Hickman

Hardwick

et al. 2005

Journal of Biological Chemistry

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One of the earliest effects of hypoxia on neuronal function is to produce a run-down of synaptic transmission, and more prolonged hypoxia results in neuronal death. An increase in the permeability of the outer mitochondrial membrane, controlled by BCL-2 family proteins, occurs in response to stimuli that trigger cell death. By patch clamping mitochondrial membranes inside the presynaptic terminal of a squid giant synapse, we have now found that several minutes of hypoxia trigger the opening of large multiconductance channels. The channel activity is induced concurrently with the attenuation of synaptic responses that occurs under hypoxic conditions. Hypoxia-induced channels are inhibited by NADH, an agent that inhibits large conductance channels produced by a pro-apoptotic fragment of BCL-xL in these synaptic mitochondria. The appearance of hypoxia-induced channels was also prevented by the caspase/cysteine protease inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone (Z-VAD-fmk), which inhibits proteolysis of BCL-xL during hypoxia. Both NADH and Z-VAD-fmk reduced significantly the rate of decline of synaptic responses during hypoxia. Our results indicate that an increase in outer mitochondrial channel activity is a very early event in the response of neurons to hypoxia and suggest that this increase in activity may contribute to the decline in synaptic function during hypoxia.

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Section: Discussionmentioning

confidence: 99%

Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse

Jonas

Hickman

Hardwick

et al. 2005

Journal of Biological Chemistry

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“…It should be noted that most of these previous reports analyzed excitatory synaptic transmission. An effect of P2 receptor agonists on inhibitory interneurons in the hippocampal slice has been described by Khakh et al (2003) in the CA1 region and suggested by Aihara et al (2002) in the dentate gyrus. Khakh et al (2003) demonstrated a facilitation of glutamate release through activation of presynaptic P2X 2 receptor channels in the CA1 interneurons.…”

Section: Activation Of Both P1 and P2 Receptors Expressed In Distinctmentioning

confidence: 93%

Direct Excitation of Inhibitory Interneurons by Extracellular ATP Mediated by P2Y₁Receptors in the Hippocampal Slice

Kawamura¹,

Gachet²,

Inoue³

et al. 2004

J. Neurosci.

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ATP is an important cell-to-cell signaling molecule mediating the interactions between astrocytes and neurons in the CNS. In the hippocampal slices, ATP suppresses excitatory transmission mostly through activation of adenosine A 1 receptors, because the ectoenzyme activity for the extracellular breakdown of ATP to adenosine is high in slice preparations in contrast to culture environments. Because the hippocampus is also rich in the expression of P2 receptors activated specifically by ATP, we examined whether ATP modulates neuronal excitability in the acute slice preparations independently of adenosine receptors. Although ATP decreased the frequency of spontaneously occurring EPSCs in the CA3 pyramidal neurons through activation of adenosine A 1 receptors, ATP concurrently increased the frequency of IPSCs in a manner dependent on action potential generation. This effect was mediated by P2Y 1 receptors because (1) 2-methylthio-ATP (2meSATP) was the most potent agonist, (2) 2Ј-deoxy-N 6 -methyladenosine-3Ј,5Ј-bisphosphate diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC frequency was not observed in the transgenic mice lacking P2Y 1 receptor proteins. Application of 2meSATP elicited MRS2179-sensitive time-and voltage-dependent inward currents in the interneurons, which depolarized the cell to firing threshold. Also, it increased [Ca 2ϩ ] i in both astrocytes and interneurons, but, unlike the former effect, the latter was entirely dependent on Ca 2ϩ entry. Thus, in hippocampal slices, in addition to activating A 1 receptors of the excitatory terminals after being converted to adenosine, ATP activates P2Y 1 receptors in the interneurons, which is linked to activation of unidentified excitatory conductance, through mechanisms distinct from those in the astrocytes.

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“…This indicated that endogenous ATP released from the hippocampus upon energy deprivation can activate various subtypes of P2X receptors to elicit glutamate overflow, therefore facilitating ischaemia-evoked glutamate excitotoxicity [28]. An opposing protective role for ATP against hypoxic/hypoglycaemic perturbation of hippocampal neurotransmission was conversely demonstrated by inhibition of neuronal activity through enhancement of GABA release via P2X receptors [29].…”

Section: Ischaemiamentioning

confidence: 99%

Membrane compartments and purinergic signalling: P2X receptors in neurodegenerative and neuroinflammatory events

et al. 2008

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ATP is a potent signalling molecule abundantly present in the nervous system, where it exerts physiological actions ranging from short‐term responses such as neurotransmission, neuromodulation and glial communication, to long‐term effects such as trophic actions. The fast signalling targets of extracellular ATP are represented by the ionotropic P2X receptors, which are broadly and abundantly expressed in neurons and glia in the whole central and peripheral nervous systems. Because massive extracellular release of ATP often occurs by lytic and non‐lytic mechanisms, especially after stressful events and pathological conditions, purinergic signalling is correlated to and involved in the aetiopathology and/or progression of many neurodegenerative diseases. In this minireview, we highlight the contribution of the subclass of ionotropic P2X receptors to several diseases of the human nervous system, such as neurodegenerative disorders and immune‐mediated neuroinflammatory dysfunctions including ischaemia, Parkinson’s, Alzheimer’s and Huntington’s diseases, amyotrophic lateral sclerosis and multiple sclerosis. The role of P2X receptors as novel and effective targets for the genetic/pharmacological manipulation of purinergic mechanisms in several neuropathological conditions is now well established. Nevertheless, any successful therapeutic intervention against these diseases cannot be restricted to P2X receptors, but should take into consideration the whole and multipart ATP signalling machinery.

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Adenosine triphosphate accelerates recovery from hypoxic/hypoglycemic perturbation of guinea pig hippocampal neurotransmission via a P2 receptor

Cited by 21 publications

References 30 publications

Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse

Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse

Direct Excitation of Inhibitory Interneurons by Extracellular ATP Mediated by P2Y₁Receptors in the Hippocampal Slice

Membrane compartments and purinergic signalling: P2X receptors in neurodegenerative and neuroinflammatory events

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Adenosine triphosphate accelerates recovery from hypoxic/hypoglycemic perturbation of guinea pig hippocampal neurotransmission via a P2 receptor

Cited by 21 publications

References 30 publications

Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse

Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse

Direct Excitation of Inhibitory Interneurons by Extracellular ATP Mediated by P2Y1Receptors in the Hippocampal Slice

Membrane compartments and purinergic signalling: P2X receptors in neurodegenerative and neuroinflammatory events

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Direct Excitation of Inhibitory Interneurons by Extracellular ATP Mediated by P2Y₁Receptors in the Hippocampal Slice